O-Desmethyltramadol
O-Desmethyltramadol
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| Systematic (IUPAC) name |
| 3-[2-(1-Amino-1-methylethyl)-1-hydroxycyclohexyl]phenol |
| Clinical data |
| Pregnancy cat. |
? |
| Legal status |
? (US) |
| Routes |
Converted Metabolite |
| Pharmacokinetic data |
| Half-life |
~ 9 h |
| Identifiers |
| CAS number |
73986-53-5 Y |
| ATC code |
? |
| PubChem |
CID 130829 |
| ChemSpider |
115703 Y |
| ChEMBL |
CHEMBL1400 N |
| Chemical data |
| Formula |
C15H23NO2 |
| Mol. mass |
249.349 g/mol |
| SMILES |
eMolecules & PubChem |
-
InChI=1S/C15H23NO2/c1-16(2)11-13-6-3-4-9-15(13,18)12-7-5-8-14(17)10-12/h5,7-8,10,13,17-18H,3-4,6,9,11H2,1-2H3 Y
Key:UWJUQVWARXYRCG-UHFFFAOYSA-N Y
|
N(what is this?) (verify)
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O-Desmethyltramadol (O-DT) is an opioid analgesic and the main active metabolite of tramadol.[1]
(+)-O-Desmethyltramadol is the most important metabolite of tramadol produced in the liver after tramadol is consumed. This metabolite is considerably more potent as a μ opioid agonist than the parent compound.[2]
Tramadol is demethylated by the liver enzyme CYP2D6[3] in the same way as codeine, and so similarly to the variation in effects seen with codeine, individuals who have a less active form of CYP2D6 ("poor metabolisers") will tend to get reduced analgesic effects from tramadol.
The two enantiomers of O-desmethyltramadol show quite distinct pharmacological profiles;[4] both (+) and (-)-O-desmethyltramadol are inactive as serotonin reuptake inhibitors,[5] but (-)-O-desmethyltramadol retains activity as a noradrenaline reuptake inhibitor[6] and so the mix of both the parent compound and metabolites produced contributes significantly to the complex pharmacological profile of tramadol.
Sale as designer drug
O-desmethyltramadol has recently been marketed as a "legal substitute" to illegal opioid drugs of abuse, either in powder form or mixed into various other preparations. One such blend sold under the brand "Krypton Kratom" and containing powdered kratom leaf (Mitragyna speciosa) laced with O-desmethyltramadol, was reportedly linked to at least 9 accidental deaths from overdose during 2010-2011.[7][8][9]
See also
References
- ^ Sevcik, J; Nieber, K; Driessen, B; Illes, P (1993). "Effects of the central analgesic tramadol and its main metabolite, O-desmethyltramadol, on rat locus coeruleus neurones". British journal of pharmacology 110 (1): 169–76. PMC 2175982. PMID 8220877. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2175982. edit
- ^ Dayer, P; Desmeules, J; Collart, L (1997). "Pharmacology of tramadol". Drugs 53 Suppl 2: 18–24. doi:10.2165/00003495-199700532-00006. PMID 9190321. edit
- ^ Borlak, J; Hermann, R; Erb, K; Thum, T (2003). "A rapid and simple CYP2D6 genotyping assay--case study with the analgetic tramadol". Metabolism: clinical and experimental 52 (11): 1439–43. doi:10.1016/S0026-0495(03)00256-7. PMID 14624403. edit
- ^ Garrido, MJ; Valle, M; Campanero, MA; Calvo, R; Trocóniz, IF (2000). "Modeling of the in vivo antinociceptive interaction between an opioid agonist, (+)-O-desmethyltramadol, and a monoamine reuptake inhibitor, (-)-O-desmethyltramadol, in rats". The Journal of pharmacology and experimental therapeutics 295 (1): 352–9. PMID 10992001. edit
- ^ Bamigbade, TA; Davidson, C; Langford, RM; Stamford, JA (1997). "Actions of tramadol, its enantiomers and principal metabolite, O-desmethyltramadol, on serotonin (5-HT) efflux and uptake in the rat dorsal raphe nucleus". British journal of anaesthesia 79 (3): 352–6. PMID 9389855. edit
- ^ Driessen, B; Reimann, W; Giertz, H (1993). "Effects of the central analgesic tramadol on the uptake and release of noradrenaline and dopamine in vitro". British journal of pharmacology 108 (3): 806–11. PMC 1908052. PMID 8467366. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1908052. edit
- ^ Arndt T, Claussen U, Güssregen B, Schröfel S, Stürzer B, Werle A, Wolf G. Kratom alkaloids and O-desmethyltramadol in urine of a "Krypton" herbal mixture consumer. Forensic Science International. 2011 May 20;208(1-3):47-52. PMID 21112167
- ^ Bäckstrom BG, Classon G, Löwenhielm P, Thelander G. Krypton--new, deadly Internet drug. Since October 2009 have nine young persons died in Sweden. (Swedish). Lakartidningen. 2010 Dec 15-21;107(50):3196-7. PMID 21294331
- ^ Kronstrand R, Roman M, Thelander G, Eriksson A. Unintentional fatal intoxications with mitragynine and O-desmethyltramadol from the herbal blend Krypton. Journal of Analytical Toxicology. 2011 May;35(4):242-7. PMID 21513619